Drug Interaction Report

MONITOR: Coadministration with potent CYP450 3A4 inducers may decrease the plasma concentrations and pharmacologic effects of selinexor, which is metabolized by the isoenzyme along with multiple UDP-glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs). However, data are unavailable and so the clinical significance of this interaction is unknown. The extent to which other, less potent inducers of CYP450 3A4 may interact with selinexor is unknown.

MANAGEMENT: Caution and clinical monitoring for reduced therapeutic efficacy are recommended with the concomitant use of selinexor with potent CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.